836 research outputs found

    The distribution of charged amino acid residues and the Ca(2+) permeability of nicotinic acetylcholine receptors: a predictive model

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    Nicotinic acetylcholine receptors (nAChRs) are cation-selective ligand-gated ion channels exhibiting variable Ca(2+) permeability depending on their subunit composition. The Ca(2+) permeability is a crucial functional parameter to understand the physiological role of nAChRs, in particular considering their ability to modulate Ca(2+)-dependent processes such as neurotransmitter release. The rings of extracellular and intracellular charged amino acid residues adjacent to the pore-lining TM2 transmembrane segment have been shown to play a key role in the cation selectivity of these receptor channels, but to date a quantitative relationship between these structural determinants and the Ca(2+) permeability of nAChRs is lacking. In the last years the Ca(2+) permeability of several nAChR subtypes has been experimentally evaluated, in terms of fractional Ca(2+) current (Pf, i.e., the percentage of the total current carried by Ca(2+) ions). In the present study, the available Pf-values of nAChRs are used to build a simplified modular model describing the contribution of the charged residues in defined regions flanking TM2 to the selectivity filter controlling Ca(2+) influx. This model allows to predict the currently unknown Pf-values of existing nAChRs, as well as the hypothetical Ca(2+) permeability of subunit combinations not able to assemble into functional receptors. In particular, basing on the amino acid sequences, a Pf > 50% would be associated with homomeric nAChRs composed by different α subunits, excluding α7, α9, and α10. Furthermore, according to the model, human α7ÎČ2 receptors should have Pf-values ranging from 3.6% (4:1 ratio) to 0.1% (1:4 ratio), much lower than the 11.4% of homomeric α7 nAChR. These results help to understand the evolution and the function of the large diversity of the nicotinic receptor family

    Who is on the Team? Exploring a Person-Centred Care Approach on an Interdisciplinary Healthcare Team, from the Healthcare Provider's Perspective

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    The purpose of this study was to gain an understanding from the perspective of healthcare providers how person-centre care ideologies are translated into day-to-day practice at an oncology center. This was a single case study, conducted at a local Oncology Center. The study included 15 interviews with healthcare providers, the analysis of 15 documents, and the keeping of a reflexive research journal. Four themes and ten sub-themes were found to represent the experiences of healthcare providers: (1) Educating with Empathy (2) Informed Personal Advocate, (3) Being the “Rock”, and (4) Progressing as a Team. This study demonstrates the roles of healthcare providers, patients and caregivers on a healthcare team committed to delivering person-centred care. It also introduces a new kind of team, a person-centred care team along with complimentary guiding principles to inform the practices of healthcare providers. This study contributes to the shift in the culture of care in oncology, where patients and caregivers are welcomed onto their healthcare team

    Data mining NHANES: Utilizing a Genetic Algorithm to Detect Correlation Between Birth Sex Ratio and Epidemiological Factors

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    In the past several decades there has been increasing research into factors that may affect the birth sex ratio of parents. These can range from nutrition to hormone levels to psychological factors. The National Health and Nutritional Examination Survey (NHANES) is a broadly encompassing governmental survey that captures some of these aspects making it a rich and easily exploitable data set for these purposes. In this study we utilize custom Perl scripts written to extract such information and attempt to find correlations using a genetic algorithm. Mothers are first identified through inferred relationships within the database. Variables are then analyzed to find any significant difference between groups of women whom have more male or female offspring. Lastly, identified variables are passed on to a genetic algorithm which attempts to find any correlation between the variables and the birth sex ratio. While our analysis did not produce any conclusive results, there were some interesting findings regarding which variables were automatically selected for in the primary analysis. Ultimately the development of the tools used in this project can be helpful in answering other questions about the NHANES data set and they can potentially be applied to other problems outside of NHANES

    Japanese Cinema as Mass Art: An Export of Mass Cinema

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    The aim of the thesis is to examine the distribution and consumption of contemporary Japanese cinema in the UK. Through the study of aesthetics it seeks to identify the ways in which content and current distribution methods suit different markets. NoĂ«l Carroll’s definition of cinema and contemporary media as ‘mass art’ has informed the way in which the thesis notes variation in film content, and forms the core methodology. The selected texts range from the post-war period (1948) with films by directors such as Akira Kurosawa, to contemporary animation cinema such as the work of Mamoru Hosada (2009). The distribution methods of these films is of particular importance as the thesis links them to the export of Japanese identity. The films are available to a UK audience via a range of distribution methods such as officially distributed DVDs, online distribution, and art house cinema exhibitions. There is an emphasis on digital distribution throughout the thesis and this is reflected through the use of texts downloaded from the internet as well as digital sources such as university encyclopaedias and e-books. Each chapter is organised around a distinctive and specified market for Japanese cinema and includes detailed textual analysis of film examples. In the final chapter, on the popularity of Japanese animation (anime), the analysis is enhanced with empirical research into online consumption groups and internet communication, given these groups’ important role in the distribution of anime outside of Japan

    Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking

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    Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di-guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling

    Inside an in-House Legal Ethics Practice

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    Effects of Kaolin and Shading Net on the Ecophysiology and Berry Composition of Sauvignon Blanc Grapevines

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    Rising temperatures in most viticultural regions are associated with a higher incidence of drastic weather circumstances such as heatwaves. The consequences are reflected in qualitative and quantitative white grapes characteristics. In fact, there is an enhancement in alcohol content and a jeopardized reduction in the aromatic potential. We performed a scientific test to assuage the bump of heatwaves and exposure of grapes on Vitis vinifera cv. “Sauvignon Blanc” with exposed vines (untreated) or with kaolin foliar treatment or with partial fruit-zone shading (shading net 30 and 70%). This work aimed to evaluate the effects of shading net (SD-30% and SD-70%) and foliar kaolin (K) treatment on physiology, technological maturity, and thiolic precursors in Italy during the 2020–2021 seasons. For this purpose, four treatments were established: SD-30% (green artificial shading net at 30%), SD-70% (green artificial shading net at 70%), K (foliar kaolin), and CTRL (no application). During the two vintages, single-leaf gas exchange appraisal, leaf temperature, berry temperature, chlorophyll fluorescence, pre-dawn, and leaf water potential were measured. Moreover, berry weight, pH, °Brix, acidity (technological maturity specifications), and the following thiolic precursors were analyzed: 3-S-glutathionylhexan-1-ol (Glut-3MH), S-4-(4-methylpentan-2-one)-L-cysteine (Cys-4MMP), and 3-S-cysteinylhexan-1-ol (Cys-3MH). SD-70% and K denoted less negative water potential, a lower berry temperature, and a higher level of all precursors than the other treatments. Acidity and sugar parameters indicated significant differences among treatments. The lower berry weight and the lower tartaric acidity were found in the CTRL treatment. In comparison, SD-70% and K showed lower and more balanced sugar contents. As a result of global warming, color shading net and kaolin have been demonstrated to be good practices to counterpoise the divergence between aromatic and technological maturity in Sauvignon Blanc grapevines
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